Treatment of arthritis with arsenoxide compounds

Abstract

The present invention provides a method of treatment and/or prophylaxis of arthritis in a vertebrate comprising administering to said vertebrate in need of said treatment and/or prophylaxis a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, optionally together with a pharmaceutically acceptable carrier, diluent or excipient, wherein said compound of formula (I) is defined as: A—(L—Y) p , wherein: A comprises at least one substantially cell-membrane impermeable pendant group; L comprises any suitable linker and/or spacer group; Y comprises at least one arsenoxide or arsenoxide equivalent; p is an integer from 1 to 10; and the sum total of carbon atoms in A and L together, is greater than 6.

1. A method of treatment and/or inhibition of arthritis in a vertebrate comprising administering to said vertebrate in need of said treatment and/or inhibition a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof, optionally together with a pharmaceutically acceptable carrier, diluent or excipient, wherein said compound of formula I is defined as:
   A—[(XBX′) n B′—Y] p   (I) 
 wherein 
 Y comprises at least one arsenoxide group; 
 n is an integer selected from 0 to 20; 
 p is an integer from 1 to 10; and wherein 
 the sum total of carbon atoms in A and (XBX′) n B′ together, is greater than 6; 
 A is selected from the group consisting of: glutathione, glucosamine, cysteinyiglycine, cysteic acid, aspartic acid, glutamic acid, lysine, and arginine, and wherein the sulfur atom of each sulfur containing compound is optionally a sulfoxide or sulfone; 
 X is selected from NR—, S(O)—, —S(O)O—, —S(O) 2 —, —S(O) 2 O—, —C(O)—, —C(S)—, —C(O)O—, C(S)O—, —C(S)S—, —P(O)(R 1 )—, —P(O)(R 1 )O—, or is absent 
 B is selected from C 1 –C 10  alkylene, C 2 –C 10  alkylene, C 2 –C 10  alkynylene, C 3 –C 10  cycloalkylene, C 5 –C 10  cycloalkylene, C 3 –C 10  heterocycloalkylene, C 5 –C 10  heterocycloalkenylene, C 6 –C 12  arylene, heteroarylene or C 2 –C 10 ; 
 X′ is selected from NR—, —O—, —S—, —Se—, —S—S—, S(O)—, —OS(O)—, OS(O)O—, —OS(O) 2 , —OS(O) 2 O—, —S(O)O—, —S(O)—, —S(O) 2 O—, —OP(O)R 1 )—, —OP(O)(R 1 )O—, —OP(O)(R 1 )OP(O)(R 1 )O—, —C(O)—, —C(S)—, —C(O)O—, C(S)O—, —C(S)S—, —P(O)(R 1 )—, —P(O)(R 1 )O—, 
 
       
         
           
           
               
               
           
         
         
            or iS absent; wherein E is O, S, Se, NR or N(R) 2   + ; and 
         
         B′ is selected from C 1 –C 10  alkylene, C 2 –C 10  alkenylene, C 2 –C 10  alkynylene, C 3 –C 10  cycloalkylene, C 5 –C 10  cycloalkenylene, C 3 –C 10  heterocycloalkylene, C 5 –C 10  heterocycloalkenylene, C 6 –C 12  arylene, and heteroarylene, or is absent; wherein 
         each R is independently selected from hydrogen, C 1 –C 10  alkyl, C 2 –C 10  alkenyl, C 2 –C 10  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 3 –C 10  heterocycloalkyl, C 5 –C 10  heterocycloalkenyl, C 6 –C 12  aryl, heteroaryl, OR 2  or C 2 –C 10  acyl; R′ is the same as R or two R′ are taken together with the nitrogen atoms to which they are attached to form a 5 or 6-membered saturated or unsaturated heterocyclic ring: 
         each R 1  is independently selected from hydrogen, C 1 –C 10  alkyl, C 2 –C 10  alkenyl, C 2 –C 10  alkynyl, C 3 –C 10  cycloalkyl, C 3 –C 10  cycloalkenyl, C 3 –C 10  heterocycloalkyl, C 5 –C 10  heterocycloalkenyl, C 6 –C 12  aryl, heteroaryl, halo, OR 2  or N(R) 2 ; 
         each R 2  is independently selected from hydrogen, C 1 –C 10  alkyl, C 2 –C 10  alkenyl, C 2 –C 10  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 3 –C 10  heterocycloalkyl, C 5 –C 10  heterocycloalkenyl, C 6 –C 12  aryl, heterocycloalkyl, or —C(O)R 5 ; 
         each R 5  is independently selected from hydrogen, C 1 –C 10  alkyl, C 2 –C 10  alkenyl, C 2 –C 10  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 3 –C 10  heterocycloalkyl, C 5 –C 10  heterocycloalkenyl, C 6 –C 12  aryl, heteroaryl, C 1 –C 10  alkoxy, C 3 –C 10  alkenyloxy, C 3 –C 10  alkynyloxy, C 3 –C 10  cycloalkyloxy, C 5 –C 10  cycloalkenyloxy, C 3 –C 10  heterocycloalkyloxy, C 5 –C 10  heterocycloalkenyloxy, C 6 –C 12  aryloxy, heteroaryloxy, C 1 –C 10  alkylthio, C 5 –C 10  alkenylthio, C 3 –C 10  alkynylthio, C 3 –C 10  cycloalkylthio, C 5 –C 10  cycloalkenylthio, C 3 –C 10  heterocycloalkylthio, C 5 –C 10  heterocycloalkenylthio, C 6 –C 12  arylthio, heteroarylthio, OH, SH or N(R) 2 ; 
         wherein for each instance that B and/or B′ is arylene, the substituents directly attached to the respective arylene rings are in a para, meta or ortho relationship, and 
         wherein each alkylene, alkenylene, alkynylene, cycloalkylene, cycloalkenylene heterocycloalkylene, heterocycloalkenylene, arylene, heteroarylene and acyl are optionally independently substituted with hydrogen, C 1 –C 10  alkyl, C 2 –C 10  alkenyl, C 2 –C 10  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 3 –C 10  heterocycloalkyl, C 5 –C 10  heterocycloalkenyl, C 6 –C 12  aryl, heteroaryl, halo, cyano, cyanate, isocyanate, OR 2a , SR 6 , nitro, arsenoxide, —S(O)R 3 , —OS(O)R 3 , —S(O) 2 R 3 , —OS(O) 2 R 3 , —P(O)R 4 R 4 , —OP(O)R 4 R 4 , —N(R′) 2 ,—NRC(O)CH 2 ) m O, —C(O)R 5 , 
       
       
         
           
           
               
               
           
         
         wherein R, R 1  and R 5  are as defined above; and 
         R 2a  is selected from hydrogen, C 1 –C 5  alkyl, C 2 –C 5  alkenyl, C 2 –C 5  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkyl, C 6 –C 12  aryl, —S(O)R 3 , —S(O) 2 R 3 , —P(O)(R 4 ) 2 , N(R) 2  or —C(O)R 5 ; 
         each R 3  is independently selected from hydrogen, C 1 –C 10  alkyl, C 2 –C 10  alkenyl, C 2 –C 10  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 3 –C 10  heterocycloalkyl, C 5 –C 10  heterocycloalkenyl, C 6 –C 12  aryl, heteroaryl, C 1 –C 10  alkoxy, C 3 –C 10  alkenyloxy, C 3 –C 10  alkynyloxy, C 3 –C 10  cycloalkyloxy, C 5 –C 10  cycloalkenyloxy, C 3 –C 10  heterocycloalkyloxy, C 5 –C 10  heterocycloalkenyloxy, C 6 –C 12  aryloxy, heteroaryloxy, C 1 –C 10  alkylthio, C 3 –C 10  alkenylthio, C 3 –C 10  alkynylthio, C 3 –C 10  cycloalkylthio, C 5 –C 10  cycloalkenylthio, C 3 –C 10  heterocycloalkylthio, C 5 –C 10  heterocycloalkenylthio, C 6 –C 12  arylthio, heteroarylthio or N(R) 2 ; 
         each R 4  is independently selected from hydrogen, C 1 –C 10  alkyl, C 2 –C 10  alkenyl, C 2 –C 10  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 3 –C 10  heterocycloalkyl, C 5 –C 10  heterocycloalkenyl, C 6 –C 12  aryl, heteroaryl, C 1 –C 10  alkyoxy, C 3 –C 10  alkenyloxy, C 3 –C 10  alkynyloxy, C 3 –C 10  cycloalkyloxy, C 5 –C 10  cycloalkenyloxy, C 3 –C 10  heterocycloalkyloxy, C 5 –C 10  heterocycloalkenyloxy, C 6 –C 12  aryloxy, heteroaryloxy, C 1 –C 10  alkylthio, C 3 –C 10  alkenylthio, C 3 –C 10  alkynylthio, C 3 –C 10  cycloalkylthio, C 5 –C 10  cycloalkenylthio, C 3 –C 10  heterocycloalkylthio, C 5 –C 10  heterocycloalkenylthio, C 6 –C 12  arylthio, heteroarylthio, halo or N(R) 2 ; 
         R 6  is selected tram C 1 –C 10  alkyl, C 2 –C 10  alkenyl, C 2 –C 10  alkynyl, C 3 –C 10  cycloalky, C 5 –C 10  cycloalkenyl, C 5 –C 10  heterocycloalkyl, C 5 –C 10  heterocycloalkenyl, C 6 –C 12  aryl, heteroaryl, C 1 –C 10  alkylthio, C 3 –C 10  alkenylthio, C 3 –C 10  alkynylthio, C 3 –C 10  cycloalkylthio, C 5 –C 10  cycloalkenylthio, C 3 –C 10  heterocycloalkylthio, C 5 –C 10  heterocycloalkenylthio, C 6 –C 12  arylthio, heteroarylthio, —S(O)R 3 , —S(O) 2 R 3  or —C(O)R 5    
         R″ is the same as R or two R′ token together with the N atom to which they are attached may form a saturated, unsaturated or aromatic heterocyclic ring system; 
         Q is selected from halogen and —S(O) 2 Q 1 ; wherein Q 1  is selected from C 1 –C 4  alkyl, C 1 –C 4  perfluoroalkyl, phenyl, or p-methylphenyl; and 
         m is an integer selected from 1 to 5; wherein the compound of formula (I) is optionally linked to a detector group. 
       
     
     
       2. The method according to  claim 1 , wherein A is glutathione. 
     
     
       3. The method according to  claim 1 , wherein p is an integer from 1 to 5. 
     
     
       4. The method according to  claim 3 , wherein p is 1. 
     
     
       5. The method according to  claim 1 , wherein:
 X is selected from the group consisting of NP—, —C(O)—, —C(S)—, —C(O)O——C(S)O—, —C(S)S—, or is absent; 
 B is selected from C 1 –C 5  alkylene, C 2 –C 5  alkenylene, C 2 –C 5  alkynylene, C 3 –C 10  cycloalkylene, C 5 –C 1 acycloalkenylene, C 2 –C 12  arylene or C 2 –C 5  acyl; 
 X′ is selected from —O—, —S—, —NR—, —S—S—, —S(O)—, —S(O) 2 —, —P(O)R 1 , —OP(O)(R 1 )—, OP(O)(R 1 )O—, —OP(O)(R 1 )OP(O)(R 1 )O—; —C(O)—, —C(S)—; —C(O)O—, —C(S)O—, —C(S)S—, —Se—, 
 
       
         
           
           
               
               
           
         
          or is absent; wherein E is O, S or N(R) 2   t ; 
         n is 0, 1 or 2; and 
         B′ is C 1 –C 5  alkylene, C 2 –C 5  alkenylene, C 2 –C 5  alkynylene, C 3 –C 10  cycloalkylene, C 5 –C 10  cycloalkenylene, C 2 –C 12  arylene or is absent; and wherein 
         each R is independently selected from hydrogen, C 1 –C 5  alkyl, C 2 –C 5  alkenyl, C 2 –C 5  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 6 –C 12  aryl, OR 2  or C 2 –C 10  acyl; 
         R′ is the same as R; 
         each R 1  is independently selected from hydrogen, C 1 –C 5  alkyl, C 2 –C 5  alkenyl, C 2 –C 5  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 6 –C 12  aryl, halo, OR 2  or N(R) 2 ; 
         each R 2  is independently selected from hydrogen, C 1 –C 5  alkyl, C 2 –C 5  alkenyl, C 2 –C 5  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 6 –C 12  aryl or —C(O)R 5 ; 
         each R 5  is independently selected from hydrogen, C 1 –C 5  alkyl, C 2 –C 5  alkenyl, C 2 –C 5  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 6 –C 12  aryl, C 1 –C 5  alkoxy, C 3 –C 5  alkenyloxy, C 3 –C 5  alkynyloxy, C 3 –C 10  cycloalkyloxy, C 5 –C 10  cycloalkenyloxy, C 6 –C 12  aryloxy, C 1 –C 5  alkylthio, C 3 –C 5  alkenylthio, C 3 –C 5  alkynylthio, C 3 –C 10  cycloalkylthio, C 5 –C 10  cycloalkenylthio, C 6 –C 12  arylthio, OH, SH or N(R) 2 ; 
         wherein each instance of arylene may have substituents A and X or X and Y in a para, meta or ortho relationship, and 
         wherein each alkylene, alkenylene, alkynylene, cycloalkylene, cycloalkenylene, arylene, and acyl are optionally independently substituted with hydrogen, C 1 –C 5  alkyl, C 2 –C 5  alkenyl, C 2 –C 5  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 6 –C 2  aryl, halo, cyanate, isocyanate, OR 2a , SR 6 , nitro, arsenoxide, —S(O)R 3 , —OS(O)R 3 , —S(O) 2 R 3 , —OS(O) 2 R 3 , —P(O)R 4 R 4 , —OP(O)R 4 R 4 , —N(R′) 2 , NRC(O)(Ch 2 ) m Q, —C(O)R 5 , 
       
       
         
           
           
               
               
           
         
         wherein R, R 1  and R 5  are as defined above; and 
         R 2a  is selected from hydrogen, C 1 –C 5  alkyl, C 2 –C 5  alkenyl, C 2 –C 5  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 6 –C 12  aryl, —S(O)R 3 , —S(O) 2 R 3 , —P(O)(R 4 ) 2 , N(R) 2  or —C(O)R 5 ; 
         each R 3  is independently selected from hydrogen, C 1 –C 5  alkyl, C 2 –C 5  alkenyl, C 2 –C 5  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 6 –C 12  aryl, C 1 –C 5  alkoxy, C 3 –C 5  alkenyloxy, C 3 –C 5  alkynyloxy, C 3 –C 10  cycloalkyloxy, C 5 –C 10  cycloalkenyloxy, C 6 –C 12  aryloxy, C 1 –C 5  alkylthio, C 3 –C 5  alkenylthio, C 1 –C 5  alkynylthio, C 3 –C 10  cycloalkylthio, C 5 –C 10  cycloalkenylthio, C 6 –C 12  arylthio or N(R) 2 ; 
         each R 4  is independently selected from hydrogen, C 1 –C 5  alkyl, C 2 –C 5  alkenyl, C 2 –C 5  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 6 –C 12  aryl, C 1 –C 5  alkoxy, C 3 –C 5  alkenyloxy, C 3 –C 5  alkynyloxy, C 3 –C 10  cycloalkyloxy, C 5 –C 10  cycloalkenyloxy, C 6 –C 12  aryloxy, C 1 –C 5  alkylthio, C 3 –C 5  alkenylthio, C 3 –C 5  alkynylthio, C 3 –C 5  cycloalkylthio, C 5 –C 5  cycloalkenylthio, C 6 –C 12  arylthio, halo or N(R) 2 ; 
         R 6  is independently selected from C 1 –C 5  alkyl, C 2 –C 5  alkenyl, C 2 –C 5  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 6 –C 12  aryl, C 1 –C 5  alkylthio, C 3 –C 5  alkenylthio, C 3 –C 5  alkynylthio, C 3 –C 10  cycloalkylthio, C 5 –C 10  cycloalkenylthio, C 6 –C 12  arylthio, —S(O)R 3 , —S(O) 2 R 2  or —C(O)R 5 , 
         R″ is the same as R: 
         Q is selected from halogen and —OS(O) 2 Q 1 ; wherein Q 1  is selected from C 1 –C 4  alkyl, C 1 –C 4  perfluoroalkyl, phenyl, p-methylphenyl; and 
         m is an integer from 1 to 5. 
       
     
     
       6. The method according to  claim 1 , wherein
 X is absent; 
 B is selected from C 1 –C 5  alkylene, C 6 –C 12  arylene or C 2 –C 5  acyl; 
 X′ is selected from —O—, —S—, —NR—, —S—S—, —S(O)—, —S(O) 2 —, —P(O)(R 1 )—, —C(O)—, —C(S)—, —C(O)O—, —C(S)O—, —S—, 
 
       
         
           
           
               
               
           
         
          or absent; wherein E is O, S or N(R) 2   + ; 
         n is 0, 1 or 2: and 
         B′ is C 1 –C 5  alkylene, C 6 –C 12  arylene or is absent; and wherein 
         each R is independently selected from hydrogen, C 1 –C 5  alkyl, C 3 –C 10  cycloalkyl, C 6 –C 12  aryl, OR 2  or C 2 –C 5  acyl; 
         R′ is the same as R; 
         each R 1  is independently selected from hydrogen, C 1 –C 5  alkyl, C 3 –C 10  cycloalkyl, C 1 –C 5  aryl, halo, OR 2  or N(R) 2 ; 
         each R 2  is independently selected from hydrogen, C 1 –C 5  alkyl, C 3 –C 10  cycloalkyl, C 6 –C 12  aryl or —C(O)R 5 ; 
         each R 5  is independently selected from hydrogen, C 1 –C 5  alkyl, C 2 –C 5  alkenyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 6 –C 12  aryl, C 1 –C 5  alkoxy, C 3 –C 5  alkenyloxy, C 3 –C 10  cycloalkyloxy, C 5 –C 10  cycloalkenyloxy, C 6 –C 12  aryloxy, C 1 –C 5  alkylthio, C 3 –C 5  alkenylthio, C 3 –C 10  cycloalkylthio, C 5 –C 10  cycloalkenylthio, C 6 –C 12  arylthio, OH, SH or N(R) 2 ; 
         wherein for each instance that B and/or B′ is arylene, the substituents directly attached to the respective arylene rings are in a para, meta or ortho relationship, and 
         wherein each alkylene, alkenylene, alkynylene, cycloalkylene, cycloallenylene, arylene, and acyl are optionally independently substituted with hydrogen, C 1 –C 5  alkyl, C 2 –C 5  alkenyl, C 2 –C 5  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 2 –C 12  aryl, halo, cyano, cyanate, isocyanate, OR 2a , SR 6 , nitro, arsenoxide, —S(O)R 3 , —OS(O)R 3 , —S(O) 2 R 3 , —OS(O) 2 R 3 , —P(O)R 4 R 4 , —P(O)R 4 R 4, —N(R″)   2 , —NRC(O)(CH 2 ) m Q, —C(O)R 5 , 
       
       
         
           
           
               
               
           
         
         wherein R, R 1  and R 5  are as defined above; and 
         R 2a  is selected from hydrogen, C 1 –C 5  alkyl, C 3 –C 10  cycloalkyl, C 6 –C 12  aryl, —S(O)R 3 , —S(O) 2 R 3 , —P(O)(R 4 ) 2  and —C(O)R 5 ; 
         each R 3  is independently selected from hydrogen, C 1 –C 5  alkyl, C 3 –C 10  cycloalkyl, C 6 –C 12  aryl, C 1 –C 5  alkoxy, C 3 –C 10  cycloalkyloxy, C 6 –C 12  aryloxy, C 1 –C 5  alkylthio, C 3 –C 10  cycloalkylthio, C 6 –C 12  arylthio or N(R) 2 ; 
         each R 4  is independently selected from hydrogen, C 1 –C 5  alkyl, C 3 –C 10  cycloalkyl, C 6 –C 12  aryl, C 1 –C 5  alkoxy, C 3 –C 10  cycloalkyloxy, C 6 –C 12  aryloxy, halo or N(R) 2 ; 
         R 6  is selected from C 1 –C 5  alkyl, C 3 –C 10  cycloalkyl, C 6 –C 12  aryl, C 1 –C 5  alkylthio, C 3 –C 10  cycloalkylthio, C 6 –C 12  arylthio, —S(O)R 3 , —S(O) 2 R 3  or —C(O)R 5 , 
         R″ is the same as R; 
         Q is selected from halogen and —OS(O) 2 Q 1 ; wherein Q 1  is selected from C 1 –C 4  alkyl, C 1 –C 4  perfluoroalkyl, phenyl, p-methylphenyl; and 
         m is 1 to 5. 
       
     
     
       7. The method according to  claim 1 , wherein
 X is absent; 
 B is selected from C 1 –C 5  alkylerie, C 6 –C 12  arylene or C 2 –C 5  acyl; 
 X′ is selected from —O—, —S—, —NR—, —C(O)—, —C(O)O—, or is absent; 
 n is 1; and 
 B′ is C 1 –C 5  alkylene, C 2 –C 12  arylene or is absent; and 
 R is selected from hydrogen, C 1 –C 5  alkyl, C 6 –C 12  aryl or C 2 –C 5  acyl; 
 wherein for each instance that B and/or B′ is arylene, the substituents directly attached to the respective arylene rings are in a para, meta or ortho relationship, and 
 wherein each alkylene, arylene, and acyl are optionally independently substituted with hydrogen, C 1 –C 5  alkyl, C 2 –C 5  alkenyl, C 2 –C 5  alkynyl, C 3 –C 10  cycloalkyl, C 5 –C 10  cycloalkenyl, C 6 –C 12  aryl, halo, cyano, cyanate, isocyanate, OR 2a , SR 6 , nitro, arsenoxide, —S(O)R 3 , —S(O) 2 R 3 , —P(O)R 4 R 4 , —N(R″) 2 , —NRC(O)(CH 2 ) m Q, —C(O)R 5 , 
 
       
         
           
           
               
               
           
         
         wherein each R is independently selected from hydrogen, C 1 –C 5  alkyl, C 6 –C 12  aryl or C 2 –C 5  acyl; 
         R 2a  is selected from hydrogen, C 1 –C 5  alkyl, C 6 –C 12  aryl, —S(O)R 3 , —S(O) 2 R 3 , —P(O)(R 4 ) 2  or —C(O)R 5 ; 
         each R 3  is independently selected from hydrogen, C 1 –C 5  alkyl, C 6 –C 12  aryl, C 1 –C 5  alkoxy, C 1 –C 5  aryloxy, C 1 –C 5  alkylthio, or C 6 –C 12  arylthio; 
         each R 4  is independently selected from hydrogen, C 1 –C 5  alkyl, C 6 –C 12  aryl, C 1 –C 5  alkoxy, C 6 –C 12  aryloxy, C 1 –C 5  alkylthio, C 6 –C 12  arylthio, halo or N(R) 2 ; 
         each R 5  is independently selected from hydrogen, C 1 –C 5  alkyl, C 6 –C 12  aryl, C 1 –C 5  alkoxy, C 6 –C 12  aryloxy, C 1 –C 5  alkylthio, C 6 –C 12  arylthio, OH, SH or N(R) 2 ; 
         R 6  is selected from C 1 –C 5  alkyl, C 6 –C 12  aryl, C 1 –C 5  alkylthio, C 6 –C 12  arylthio, —S(O)R 3 , —S(O) 2 R 3  or —C(O)R 5 , 
         R″ is the same as R above; 
         Q is selected from halogen and —OS(O) 2 Q 1 ; wherein Q 1  is selected from C 1 –C 4  alkyl, C 1 –C 4  perfluoroalkyl, phenyl, p-methylphenyl; and 
         m is 1 to 5. 
       
     
     
       8. The method according to  claim 1 , wherein
 X is absent; 
 B is C 2 –C 5  acyl; 
 X′ is NR; 
 n is 1; 
 B′ is phenylene; and 
 R is H; 
 wherein the substituents directly attached to the phenylene rings are in a para-, meta- or ortho- relationship. 
 
     
     
       9. The method according to  claim 1 , wherein the compound is represented by Formula III: 
       
         
           
           
               
               
           
         
          and wherein 
         R 7  to R 10  are independently selected from the group consisting of: hydrogen, C 1 –C 5  alkyl, C 6 –C 12  aryl, halogen, hydroxy, amino, nitro, carboxy, C 1 –C 5  alkoxy, —OS(O) 2 R 3 or —NHC(O)CH 2 Q wherein Q is halogen, —OS(O) 2 CH 3 , —OS(O) 2 C 6 H 5  or —OS(O) 2 -p tolyl. 
       
     
     
       10. The method according to  claim 9 , wherein R 7  to R 10  are independently selected from hydrogen, halogen, hydroxy, amino, nitro, carboxy, C 1 –C 5  alkoxy, methyl, ethyl, iso-propyl, tert-butyl, phenyl, and —NHC(O)CH 2 Q wherein Q is halogen, —OS(O) 2 CH 3 , -—OS(O) 2 C 6 H 5 , or —OS(O) 2 -p-tolyl. 
     
     
       11. The method according to  claim 9 , wherein the arsenoxide (—As═O) group is at the 4-position of the phenylene ring. 
     
     
       12. The method according to  claim 1 , wherein the compound is 4-(N-(S-glutathionylacetyl)amino)phenylarsenoxide (GSAO) and is represented by Formula V: 
       
         
           
           
               
               
           
         
       
     
     
       13. The method according to  claim 1 , wherein the compound is represented by Formula VI: 
       
         
           
           
               
               
           
         
         wherein Q is any halogen. 
       
     
     
       14. The method according to  claim 1 , wherein the compound is represented by Formula VII: 
       
         
           
           
               
               
           
         
         wherein G is selected from the group consisting of: hydrogen, halogen, hydroxy, amino, nitro, carboxy, C 1 –C 5  alkoxy, C 1 –C 5  alkyl and C 6 –C 12  aryl and —NHC(O)CH 2 Q wherein Q is halogen, —OS(O) 2 CH3, —OS(O) 2 C 6 H 5  or —OS(O) 2 -p tolyl. 
       
     
     
       15. The method according to  claim 14 , wherein G is selected from the group consisting of: hydrogen, halogen, hydroxy, amino, nitro, carboxy, C 1 –C 5  alkoxy, methyl, ethyl, iso-propyl, tert-butyl, phenyl, and —NHC(O)CH 2 Q wherein Q is halogen, —OS(O) 2 CH 3 , —OS(O) 2 C 6 h 5  or —OS(O) 2 -p tolyl. 
     
     
       16. The method according to  claim 14 , wherein G is selected from the group consisting of hydroxy, fluorine, amino, and nitro. 
     
     
       17. The method according to  claim 1 , wherein said compound is linked to a detector group. 
     
     
       18. The method according to  claim 17 , wherein said detector group is selected from the group consisting of: fluorophore, biotin, a radionucleotide, fluorescein, and a group comprising a transition element. 
     
     
       19. The method according to  claim 17 , wherein the detector group is biotin. 
     
     
       20. The method according to  claim 18 , wherein the radionucleotide is selected from the group consisting of  3 H,  14 C,  32 P,  33 P,  35 S,  125 I,  131 I,  123 I,  111 In,  105 Rh,  153 Sm,  67 Cu,  67 Ga,  166 Ho,  177 Lu,  186 Re,  188 Re, and  99m Tc. 
     
     
       21. The method according to  claim 20 , wherein the radionucleotide is selected from the group consisting of  3 H and  14 C. 
     
     
       22. The method of  claim 1 , wherein the arthritis is selected from the group consisting of: calcific periarthritis, enteropathic arthritis, chronic arthritis, gout, hand osteoarthritis, hip arthritis, knee osteoarthritis, thumb arthritis, Jaccoud's arthritis, juvenile osteoarthritis, oligoarthritis, polyarthritis, peripheral arthritis, psoriatic arthritis, rheumatoid arthritis and septic arthritis.